Use of a catheter to deliver a therapeutic agent to the brain (e.g., into the intracerebroventricular (ICV), intrathecal, or intraparenchymal (IPA) space) generally involves the insertion of the catheter into the cranial cavity via a burr hole. The catheter may be inserted until a therapy delivering catheter tip is positioned at a predetermined target site, after which the therapeutic agent may be dispensed through the catheter in accordance with a desired therapy profile.
During a typical implantation procedure, an incision is made in the scalp to expose the patient's skull. After forming the burr hole through the skull, the catheter may be inserted into the brain. To accurately place the catheter, surgeons may use stereotactic apparatus/procedures in a process referred to as framed stereotaxy. In framed stereotaxy, a ring-like frame is mounted to the patient's skull by pins or screws. The ring-like frame is then used to determine a three-dimensional data set, from which coordinates for the target site may be calculated. Various components and instruments may be utilized with the stereotactic apparatus to assist in guiding the catheter tip to the target site.
Once the catheter tip is implanted at the target site, an opposite or protruding portion of the catheter (i.e., that portion that remains outside of the skull) may be anchored relative to the burr hole, e.g., via a burr hole anchor surgically attached to the skull. An end of the protruding portion of the catheter may then be connected, often via a secondary catheter, to a reservoir containing the therapeutic agent. After the secondary catheter is connected and tunneled beneath the skin to the reservoir, the scalp incision(s) may be closed and the system may deliver therapy in accordance with the desired profile.
As one can appreciate, implantation of a catheter within the brain, via framed stereotaxy procedures or otherwise, may present problems. For instance, the process of physically attaching the catheter to the burr hole anchor may inadvertently impart loads to the catheter that are capable of displacing the catheter tip relative to the target site. Depending on the application, even slight displacement of the tip may result in reduced therapeutic efficacy.
Moreover, for some therapeutic agents, e.g., those of higher molecular weight, delivery to the brain may be hampered by fluid pressure within the brain. In some instances, this fluid pressure may allow blood to enter the catheter tip and travel upwardly into the catheter. To address this issue, the reservoir may be configured as a pressurized infusion pump to provide convection enhanced delivery (CED) of the therapeutic agent.
While CED may address some instances of reverse fluid flow during drug infusion, blood entry into the catheter tip may still occur, e.g., after the catheter is implanted but before it is connected to the infusion pump. Depending on the catheter construction and the time period between implantation and the start of infusion, any blood that has entered the catheter may ultimately clot, potentially interfering with, or even blocking, subsequent delivery of the therapeutic agent.